Scientists have new data which they believe identifies a mechanism that could circumvent artemisinin resistance. [Kokhanchikov/Fotolia]
Scientists have new data which they believe identifies a mechanism that could circumvent artemisinin resistance. [Kokhanchikov/Fotolia]

With almost 50% of the world’s population living in regions endemic to malaria, understanding the mechanisms that underlie drug-resistance is imperative for controlling a disease that has been decimating human populations since the Stone Age.

Currently, the last-line of defense against the deadliest strain of malaria, Plasmodium falciparum, is a drug, originally derived from Chinese traditional medicine, called artemisinin (ART). Since using ART in a more widespread effort several years ago to control the parasitic infection, resistance to the drug has emerged within six countries of Southeast Asia. If the rate of resistance continues to grow and spreads to Africa, which is home to the greatest number of malaria cases, many countries could face an unprecedented health crisis.     

However, a collaborative group led by researchers from the University of Melbourne, has new data which they believe identifies a mechanism that could circumvent ART resistance.     

The findings from this study were published recently in PLoS Biology through an article entitled “Targeting the Cell Stress Response of Plasmodium falciparum to Overcome Artemisinin Resistance.”

Utilizing current research that shows artemisinins function by chemically damaging the malaria parasite’s proteins, causing them to activate a cellular stress response pathway, the Melbourne researchers developed a method for predicting parasite clearance in vitro.

“Our detailed kinetic observations are used to develop a mathematical model that allows, for the first time, a simulation of parasite responses to artemisinin chemotherapy in patients,” explained Leann Tilley, Ph.D., professor of biochemistry and molecular biology at the University of Melbourne and senior author on the current study.

Dr. Tilley and her colleagues observed that the responses of resistant and sensitive parasites to ART revealed that drug treatment slows parasite growth and targets proteins for degradation by the cell’s garbage bin, the proteasome. However, the researchers noted that resistant parasites had fewer proteins primed for degradation than sensitive parasites—suggesting that artemisinin-resistant parasites are better able to respond to the damage inflicted by ART.

Interestingly, the researchers noted that despite the improved response they were able to overcome and kill the parasites by either extending the artemisinin treatment or by using a combination therapy with proteasome inhibitors, which caused the accumulation of damaged proteins and increased cellular stress.

“By disabling the malaria parasite's increased defence system, the antimalarial medications can work more effectively on patients,” said Dr. Tilley. “We found that while resistant parasites are much better at surviving ART treatment than sensitive parasites, extending the ART treatment or adding a very low concentration of an anticancer drug is enough to completely reverse the resistance mechanism.”

The malaria researchers were very encouraged by their findings, but urge continued vigilance in developing new drug therapies and strategies, in order to control the disease and prevent further drug-resistance.

“Malaria continues to kill more than half a million children every year and its treatment relies heavily on a single drug class. We need to ensure that these drugs keep working by outsmarting the resistance mechanism,” concluded Professor Tilley.

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